Skip to main content
SpringerLink
Log in

The significance of p53 mutations as an indicator of the biological behavior of recurrent hepatocellular carcinomas

  • Original Articles
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

The significance of p53 mutations in the primary lesion for recurrent hepatocellular carcinoma (HCC) was evaluated. Mutations of p53 were examined using non-radioisotopic (nonRI)-polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) in 98 resected HCCs. Of the 98 cases, 25 (26%) had a p53 mutation. In 83 patients who survived surgery, the presence of a p53 mutation was associated with a shortened overall survival (P<0.001) and a shortened cancer-free survival (P<0.05). In 43 patients who developed recurrence, there was no statistically significant correlation between the status of p53 in the primary lesion and the clinical features of recurrent HCCs examined, i.e., extrahepatic metastasis, the number of recurrent tumors, extent of recurrent tumors, and treatment for recurrent tumors. However, postrecurrence survival was significantly lower in patients in whom a p53 mutation had been detected in the primary lesion (P<0.01). A multivariate analysis for prognostic value after recurrence revealed that the p53 mutation was a useful independent prognostic factor affecting survival after recurrence (P<0.01). In conclusion, our findings suggest that HCCs with p53 mutations have a high malignant potential based on their poor prognosis. Therefore, a p53 mutation in the primary lesion is useful as an indicator of the biological behavior of recurrent HCCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ikeda K, Saitoh S, Tsubota A, Arase Y, Chayama K, Kumada H, Watanabe G, Tsurumaru M (1993) Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma. Cancer 71:19–25

    Article  CAS  PubMed  Google Scholar 

  2. Ebara M, Ohto M, Sugiura N, Kita K, Yoshikawa M, Okuda K, Kondo F, Kondo Y (1990) Percutaneous ethanol injection for the treatment of small hepatocellular carcinoma. Study of 95 patients. J Gastroenterol Hepatol 5:616–626

    Article  CAS  PubMed  Google Scholar 

  3. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, Tuinen PV, Ledbetter DH, Baker DF, Nakamura Y, White R, Vogelstein B (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221

    Article  CAS  PubMed  Google Scholar 

  4. Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell 57:1083–1093

    Article  CAS  PubMed  Google Scholar 

  5. Shieh YSC, Nguyen C, Vocal MV, Chu HW (1993) Tumor suppressor p53 gene in hepatitis C and B virus-associated human hepatocellular carcinoma. Int J Cancer 54:558–562

    Article  CAS  PubMed  Google Scholar 

  6. Nishida N, Fukuda Y, Kokuryu H, Toguchida J, Yandell DW, Ikenega M, Imura H, Ishizaki K (1993) Role and mutational heterogeneity of the p53 gene in hepatocellular carcinoma. Cancer Res 53:368–372

    CAS  PubMed  Google Scholar 

  7. Bressac B, Kew M, Wands J, Ozturk M (1991) Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature 350:429–431

    Article  CAS  PubMed  Google Scholar 

  8. Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC (1991) Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 350:427–428

    Article  CAS  PubMed  Google Scholar 

  9. Hsu HC, Tseng HJ, Lai PL, Lee PH, Peng SY (1993) Expression of p53 gene in 184 unifocal hepatocellular carcinomas: association with tumor growth and invasiveness. Cancer Res 53:4691–4694

    CAS  PubMed  Google Scholar 

  10. Hayashi H, Sugio K, Matsumata T, Adachi E, Takenaka K, Sugimachi K (1995) The clinical significance of p53 gene mutation in hepatocellular carcinomas from Japan. Hepatology 22:1702–1707

    CAS  PubMed  Google Scholar 

  11. Liver Cancer Study Group of Japan (1992) The general rules for the clinical and pathological study of primary liver cancer, 3rd edn. (in Japanese). Kanehara, Tokyo

    Google Scholar 

  12. Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 86:2766–2770

    Article  CAS  PubMed  Google Scholar 

  13. Oto M, Miyake S, Yuasa Y (1993) Optimization of nonradioisotopic single strand conformation polymorphism analysis with a conventional minislab gel electrophoresis apparatus. Anal Biochem 213:19–22

    Article  CAS  PubMed  Google Scholar 

  14. Oda T, Tsuda H, Scarpa A, Sakamoto M, Hirohashi S (1992) p53 gene mutation spectrum in hepatocellular carcinoma. Cancer Res 52:6358–6364

    CAS  PubMed  Google Scholar 

  15. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53

    Article  CAS  PubMed  Google Scholar 

  16. Barnes WM (1994) PCR amplification of up to 35-kb DNA with high fidelity and high yield from λ bacteriophage templates. Proc Natl Acad Sci USA 91:2216–2220

    Article  CAS  PubMed  Google Scholar 

  17. Tanaka S, Toh Y, Adachi E, Matsumata T, Mori R, Sugimachi K (1993) Tumor progression in hepatocellular carcinoma may be mediated by p53 mutation. Cancer Res 53:2884–2887

    CAS  PubMed  Google Scholar 

  18. Shi CY, Phang TW, Lin Y, Wee A, Li B, Lee HP, Ong CN (1995) Codon 249 mutation of the p53 gene is a rare event in hapatocellular carcinomas from ethnic Chinese in Singapore. Br J Cancer 72:146–149

    CAS  PubMed  Google Scholar 

  19. Kikuchi Y, Kishi T, Suzuki M, Furusato M, Aizawa S (1994) Polymerase chain reaction-single strand conformation polymorphism analysis of the p53 gene in paraffin-embedded surgical material from human renal cell carcinomas. Virchows Arch 424: 229–233

    Article  CAS  PubMed  Google Scholar 

  20. Kakeji Y, Korenaga D, Tsujitani S, Baba H, Anai H, Maehara Y, Sugimachi K (1993) Gastric cancer with p53 overexpression has high potential metastasising to lymph nodes. Br J Cancer 67:589–593

    CAS  PubMed  Google Scholar 

  21. Ackerman NB, Nallathambi MN, Patel KR, Panchacharam P, Williams SE (1986) Second hepatoma developing 13 years after resection of first tumor. Arch Surg 121:726–728

    CAS  PubMed  Google Scholar 

  22. Kumada T, Nakano S, Takeda I, Sugiyama K, Osada T, Kiriyama S, Toyoda H, Takahashi M (1995) Clinical evaluation of a recurrent mode after treatment in patients with small hepatocellular carcinoma (in Japanese with English abstract). Nippon Shokakibyo Gakkai Zasshi (Jpn J Gastroenterol) 92:1258–1265

    CAS  PubMed  Google Scholar 

  23. Shuto T, Kinoshita H, Hirohashi K, Kubo S, Iwasa R, Kubota D, Wakasa K, Yamamoto T, Sakurai M (1993) Clinicopathological analysis of the patients who had plural hepatic resections for hepatocellular carcinoma (in Japanese with English abstract). Nippon Shokaki Geka Gakkai Zasshi (Jpn J Gastroenterol Surg) 26:809–814

    Google Scholar 

  24. Matsuda Y, Ito T, Oguchi Y, Nakajima K, Izukura T (1993) Rationale of surgical management for recurrent hepatocellular carcinoma. Ann Surg 217:28–34

    Article  CAS  PubMed  Google Scholar 

  25. Nagao T, Kondo F, Sato T, Nagao Y, Kondo Y (1995) Immunohistochemical detection of aberrant p53 expression in hepatocellular carcinoma: correlation with cell proliferative activity indices, including mitotic index and MIB-1 immunostaining. Hum Pathol 26:326–333

    Article  CAS  PubMed  Google Scholar 

  26. Saegusa M, Takano Y, Kishimoto H, Wakabayashi G, Nohga K, Okudaira M (1993) Comparative analysis of p53 and c-myc expression and cell proliferation in human hepatocellular carcinomas—an enhanced immunohistochemical approach. J Cancer Res Clin Oncol 119:737–744

    Article  CAS  PubMed  Google Scholar 

  27. Lowe SW, Ruley HE, Jacks T, Housman DE (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967

    Article  CAS  PubMed  Google Scholar 

  28. Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, Housman DE, Jacks T (1994) p53 status and the efficacy of cancer therapy in vivo. Science 266:807–810

    Article  CAS  PubMed  Google Scholar 

  29. Bergh J, Norberg T, Sjögren S, Lindgren A, Holmberg L (1995) Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy. Nat Med 1:1029–1034

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Second Department of Surgery, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan

    Hiroyuki Sugo, Shigeru Takamori, Kuniaki Kojima, Tomoe Beppu & Shunji Futagawa

Authors
  1. Hiroyuki Sugo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shigeru Takamori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kuniaki Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomoe Beppu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shunji Futagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugo, H., Takamori, S., Kojima, K. et al. The significance of p53 mutations as an indicator of the biological behavior of recurrent hepatocellular carcinomas. Surg Today 29, 849–855 (1999). https://doi.org/10.1007/BF02482774

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02482774

Key Words

Search

Navigation